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OESOPHAGEAL CANCER Co-convened by AORTIC and NCI

Tracks
STREAM 2
Tuesday, November 9, 2021
7:30 PM - 8:45 PM
STREAM 2

Speaker

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Dr Clement Narh
International Agency for Research on Cancer (IARC)

AN AFRICAN ESOPHAGEAL SQUAMOUS CELL CARCINOMA RISK PREDICTION MODEL AND RISK SCORE DECOMPOSITION PROFILE: THE ESCAPE CASE-CONTROL STUDIES

Abstract

Background: Risk prediction models for esophageal squamous cell carcinoma (ESCC) have been developed in China, Iran, Japan, Sweden and Norway, but not yet for Africa’s ESCC corridor. In the present study, our aims were: (i) to develop an ESCC risk score for East/Southern Africa based on easy-to-ascertain risk factors and (ii) decompose the risk score into contributing factors.
Methods: Analyses consisted of four steps. (1) Relative risks (RR), estimated as mutually-adjusted odds ratios, were generated from an ESCC case-control study in Kenya, Tanzania and Malawi, of 1279 cases and 1346 controls. Criteria for the inclusion of risk factors were ease-of-assessment and association with ESCC risk substantiated by consistent effects across countries. (2) The model’s discriminatory accuracy and calibration were assessed using AUC statistics. (3) A risk score decomposition was conducted by quintiles of country and sex-specific relative risks score in controls. (4) Absolute 5-year risk of ESCC were predicted for Kenya, by incorporating population-based incidence rates.
Results: In addition to age, sex and country, the risk prediction model included six risk factors: tobacco use (never, 1<10 cigarettes per day or smokeless tobacco users, 10+ cigarettes/day), alcohol (never, beers/wines only, drinker including of spirits), thermal exposure index (TEI), number of missing teeth, sleeping by fire and educational level. The model had good discrimination [AUC = 0.74; 95% confidence interval, 95% CI (0.70, 0.78)]. In the sex-specific models, the c-statistic in men was higher [AUC = 0.78; 95% CI (0.75, 0.80)] than women [AUC = 0.67; 95% CI (0.64, 0.71)].
Conclusion: This practical African risk prediction model of ESCC showed good discrimination to identifying individuals at high risk of ESCC. It may enrich aetiologic research and early detection in this setting.
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Dr Gwinyai Masukume
Environment and Lifestyle Epidemiology Branch, International Agency for Research On Cancer, World Health Organization

HOT BEVERAGES AND PORRIDGE AND OESOPHAGEAL CANCER RISK IN MALAWI AND TANZANIA: A CASE-CONTROL STUDY

Abstract

Introduction
Consumption of very hot beverages/food is a probable carcinogen and might contribute to the African corridor of esophageal squamous cell carcinoma (ESCC). We investigated ESCC risk in relation to several measures of possible thermal injury individually and as a composite score.
Methods
We conducted ESCC case–control studies in Blantyre, Malawi (2017-20) and the Kilimanjaro region, Tanzania (2015-19). Using logistic regression models adjusted for country, age, sex, alcohol and tobacco, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for self-reported metrics of tea, coffee and porridge consumption.
Results
The study included 849 cases and 906 controls. Three metrics were positively associated with ESCC risk: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for ‘very hot’ vs ‘hot’), waiting time before drinking/eating (1.76 (1.37, 2.26) for < 2 vs 2-5 minutes) and drinking/eating speed (2.23 (1.78, 2.79) for ‘normal’ vs ‘slow’ consumers). Self-reported mouth burning was not associated with risk. The composite score indicated that ESCC risk increased, OR of 3.60 (1.99, 6.51) for a score of 7+ vs 2.
Conclusions
Consumption of hot foods/beverages is a potentially modifiable ESCC risk factor in Malawi and Tanzania. These findings suggest a new composite exposure metric for use in future studies.
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Dr Michael Mwachiro
Tenwek Hospital

INDOOR WOOD COMBUSTION, CARCINOGENIC EXPOSURE AND ESOPHAGEAL CANCER IN SOUTHWEST KENYA

Abstract

Objective: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been shown to be a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil. However, PAH assessments have not been conducted in East Africa which is an ESCC hot spot. This study aimed to evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions.

Methods: in this study funded by AORTIC's Beginning Investigator Catalytic Grant (BIGCAT), we recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD.

Results: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD.

Conclusions: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. This study highlights the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.
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Dr Violet Kayamba
University of Zambia

Risk factors for oesophageal cancer in Zambia: a case-control study

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Dr Bongani Kaimila
Unc Project

HIV AND OTHER RISK FACTORS FOR OESOPHAGEAL SQUAMOUS CELL CARCINOMA IN MALAWI

Abstract

Objective: esophageal cancer (EC) is the second commonest cancer in Malawi. EC is classified as esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). 95% of all disease in Malawi is ESCC. Despite such a high burden, very little is known about the epidemiology of ESCC in Malawi. We conducted a study to describe the risk factors for ESCC in Malawi.
Methods: we conducted a case-control study from 1st August 2017 to 4th April 2020 at a large teaching hospital and a regional hospital in Lilongwe Malawi. Adults 18 years and above with confirmed ESCC or clinically suspected ESCC were enrolled as cases. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls (selected from patients or their guardians in orthopedic, dental and ophthalmology wards) were frequency matched by age range, region of origin and gender. A mobile-based structured questionnaire delivered by a trained interviewer was the main method of data collection. Conditional logistic regression models were used to assess the effect of different risk factors on ESCC. Data analysis was done in Stata 15.
Results: 300 cases and 300 controls were enrolled into the study. Median age of cases was 56 years and median age of controls was 56 years. 186 (62%) cases were male, with a male:female ratio of 1.6:1. 33 (11%) cases were HIV+ while 12 (4%) controls were HIV+. HIV positivity had an adjusted odds ratio of 4.0 (95% CI 1.8-9.0 p=0.001) for ESCC. 89 (30%) cases were ever smokers while 65 (22%) controls were ever smokers. Smoking had an adjusted odds ratio of 2.4 (95% CI 1.4-4.2 p=0.003) for ESCC.
Conclusion: Vigorous public health messaging to address the modifiable risk factors identified in this study can help to reduce the burden of ESCC in Malawi.
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Mr Wenlong Chen
National Cancer Registry, National Health Laboratory Service

GENOME-WIDE ASSOCIATION STUDY OF AFRICAN OESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract

Objective:
Esophageal squamous cell carcinoma (ESCC) has a high incidence in sub-Saharan Africa but little is known about the genetic contribution to ESCC susceptibility in this region. We carried out a genome-wide association study (GWAS) in the South African Black (SAB) population to identify genetic risk factors for African ESCC.

Methods:
Samples from 1,686 OSCC cases and 3,217 population controls were genotyped on the 2.3 million H3 Africa SNP Illumina array and additional SNPs imputed using the Wellcome Sanger Institute imputation service. After correction for population substructure, the final imputed dataset of 14.4M SNPs was used in linear-mixed model analysis, using GEMMA to test for association. A meta-analysis with 4.85 million SNPs common to both our study and a GWAS of 2,013 Chinese ESCC cases and 2,701 controls was done using METAL.

Results:
The ESCC GWAS in the SAB population identified a total of 62 SNPs from 29 independent potential risk loci showing suggestive association with ESCC (P<5x10-6). Association signals at or near genome-wide significance were observed upstream of the FAM120A gene on chromosome 9 (rs12379660, p=4.58x10-8), and in a region spanning the MYO1B and STAT4 genes on chromosome 2 (rs142741123, p=5.49x10-8) with SNPs unique to African populations. In the meta-analysis, 12 SNPs were associated with ESCC at genome-wide significance. These included rs12379660 (chr9: p-value_meta=9.36x10-10), which is the novel locus identified in our African ESCC GWAS, rs7099485 (chr10: p-value_meta=1.48x10-8) in PLCE1, and rs1033667 (chr22: p-value_meta=1.47x10-9) in CHEK2.

Conclusions:
This study is, to our knowledge, the first cancer GWAS conducted in a resident African population and has detected two novel risk loci for ESCC, one of which is likely specific to African populations. It also demonstrates the power of trans-ethnic meta-analysis to identify common or distinct risk loci in populations of diverse ancestry.
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Dr Jason Nomburg
Dana-Farber Cancer Institute

AN INTERNATIONAL REPORT ON BACTERIAL COMMUNITIES IN OESOPHAGEAL SQUAMOUS CARCINOMA

Abstract

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.
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Dr Alita Mrema
Ocean Road Cancer Institute

TREATMENT OUTCOMES OF OESOPHAGEAL CANCER IN TANZANIA

Abstract

BACKGROUND: Esophageal cancer (EC) is a leading cause of cancer morbidity and mortality in Tanzania. This study aims to investigate the overall survival and quality of life (QoL) of EC patients undergoing treatment with chemotherapy, radiotherapy, and chemoradiation. METHODS: This study presents results from a single-center analysis from an international, multicenter, prospective, observational cohort study of adult patients diagnosed with EC in Eastern Africa (The TOEC-Eastern Africa Study). This study was conducted at Ocean Road Cancer Institute. Enrollment began in May 2019 and continues to date. Consecutive patients with EC who received treatment with chemotherapy, radiotherapy, and chemoradiation were included in the analysis. QoL was assessed using the Modified Rosenblatt Index at study enrollment, one- and three months following treatment and then every three months through death or loss to follow up. The log-rank test was used to compare six-month overall survival (OS) by treatment. T-test was used to compare mean change in QoL metrics from baseline at one-, three- and six months. RESULTS: 201 patients were enrolled (radiation n=140, chemoradiation n=51, chemotherapy n=10). Median age was 59 years; 70% were male. 91% had squamous cell carcinoma. Median baseline dysphagia score was three. Six-month OS by treatment was: chemotherapy 76%, radiation 85%, and chemoradiation 94% (log-rank p=0.160). In the chemoradiation and radiation arms, mean dysphagia scores improved significantly as compared to baseline (chemoradiation: one-month -0.65 (standard deviation (SD) 0.91) p=<0.001, three-months -0.95 (SD 0.85) p=<0.001, six-months -1.19 (SD 0.79) p=<0.001; radiation: one-month -0.47 (SD 1.06) p=<0.001, three-months -0.56 (SD 1.16) p=<0.001, six-months -0.43 (SD 1.24) p=0.0145). In chemotherapy arm, dysphagia scores did not differ significantly from baseline at any of the three time points. CONCLUSIONS: Preliminary results suggest comparable six-month OS across treatment arms. Radiation-based treatments are associated with improvements in dysphagia scores.
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Dr Sarah Nyagabona
Muhimbili University of Health and Allied Sciences

Evaluation of supportive care needs among oesophageal cancer patients receiving palliative radiotherapy at Ocean Road Cancer Institute in Tanzania

Abstract

EVALUATION OF SUPPORTIVE CARE NEEDS AMONG ESOPHAGEAL CANCER PATIENTS RECEIVING PALLIATIVE CARE AT OCEAN ROAD CANCER INSTITUTE.
OBJECTIVE: Ocean Road Cancer Institute attends more than 700 new cases of esophageal cancer, accounting to 10% of all new annual cases at the center. Most of the patients come with advanced disease stages requiring supportive care, which integrates the provision of physical, psychological, spiritual, and practical needs of patients and their families. We aimed to assess supportive care needs among these patients receiving palliative radiotherapy at the center.
METHOD: We conducted a prospective observational study in which patients with esophageal cancer in palliative care were recruited and were followed up for. Summative scales of various aspects of supportive care needs were generated and scale reliability examined using Cronbach’s Alpha.
RESULTS: A total of 28 participants were recruited with the median age of 58 years (Interquartile range (IQR (46-68)). Majority of the participants were males 75.00% and more than one third of the patients were self-employed (46.43%).Also the median body mass index(BMI) of participants was 23.6(IQR 21.6-25.2)kg/m2.About 44.8% of patients who were treated had no health insurance and 42.86% were deceased at the end of the study. All patients had difficulties in diet, mean scale of 4 (S.E; 0.139). All EC patients were in need of emotional, practical, spiritual, and social support. Above 95% were observed to need psychological support and more than three quarter of patients 85.71% were in need of information on supportive care.
CONCLUSION: The demands for supportive care among patients with esophageal cancer on palliative care is high and varies by age and gender. There is a need of creating a comprehensive palliative care framework that addresses more that oncological directed care but also in cooperating emotional, psychological, practical, social and emotional supportive needs in our resource limited settings.

Facilitators

Valerie Mccormack
International Agency for Research Cancer

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Michael Mwachiro
Tenwek Hospital

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